Published in Panorama
Fever of Unknown Origin
One week into the fever, doctors were unable to pinpoint the cause of Siddharth’s fever. Basic medical evaluation yielded nothing positive and there were no accompanying symptoms suggestive of any particular illness. A further two weeks of tests for various illnesses returned nothing positive. Siddharth’s family was worried. The doctors finally decided to give him Anti Tuberculosis Treatment (ATT). The result was dramatic and within a week Siddharth seemed to respond. On the advice of his doctor, he completed the ATT course of seven months, involving treatment with a battery of four drugs.
Fever of unknown origin (FUO) or Pyrexia of Unknown Origin (PUO) as the condition is called, happens in some cases, say Drs.A. H.O.Mousa and Kishan Pakkal, Consultants, Internal Medicine, Zulekha Hospital, Sharjah. Dr.Mousa explains, “It is a condition in which the temperature hovers around 38.3 degrees Celsius (101 degree Fahrenheit) or more, on several occasions, lasting for three weeks or more and there is failure to reach a conclusive diagnosis as to its cause. Even after once week of inpatient investigation, we are not able to reach any definite diagnosis as to the cause of fever.”
And FUO can happen to anybody regardless of age, sex or any other factor, says Dr.Pakkal. While generally in children, bacterial or viral infections are the most common causes of FUO, in adults, the cause of fever could be attributed to connective tissue disorders or malignant growth anywhere in the body. “There is no risk factor that we can identify. However, with so much of advanced technology, in very rare instances it happens that the fever defies diagnosis.”
According to the doctors, FUO can categorically be caused due to infections – bacterial or viral, to connective tissue disorders like lupus, rheumatoid arthritis and other disorders, malignancy as in leukemia, lymphoma, low white blood count, HIV/AIDS and also due to drugs.
Explaining the course of action when patients come in complaining of fever, Dr.Mousa clarifies, “When a patient first presents with fever, with or without attending symptoms, we first look for the common causes, which is infection – bacterial or viral. We do a complete and careful history of the patient, seeking to get his past medical history, his diet regimen, travel details since he could have visited regions where malaria, typhoid, tuberculosis, yellow fever or other diseases may be prevalent. We look for some regular pattern to the fever; for instance, intermittent fever with shivering may be indicative of malaria. Very often, even deep seated abscess may be the reason for fever. In this instance, the fever is of a swinging nature with regular patterns of high and low temperatures. So we investigate with X ray or ultrasound. Based on history taking we conduct some preliminary tests which may include taking blood count, liver and renal function test, urine examination and blood culture.”
Dr.Pakkal adds, “In searching for an infectious cause, we do skin and other screening tests for diseases such as tuberculosis, malaria, typhoid and others. If we find the antibody levels to a number of infectious agents rising, they suggest an active infection. Based on these findings we treat the patients.”
Dr.Mousa adds, “We sometimes repeat the initial examinations for a second time because sometimes the patients come in the first week with only fever and no accompanying symptoms. But after another week, some new symptoms may show up which may indicate further tests for a specific, suspected disease.”
“Where all possible tests return negative and the patient does not suffer from infection, Dr.Pakkal explains, “sometimes in countries like India, we label the condition as Tuberculosis (TB) and just start the patient on Anti TB Treatment (ATT), a 4-drug regime and we find the patients responding remarkably. We presume probably that it may be TB because in the tropical setup, it is very common for somebody to have it.”
But, is it not possible to diagnose TB in the first instance? “Yes, it is possible, but sometimes there are times when it does not come in the blood picture initially since it is so deep seated that it does not even show up in an Xray,” says Dr.Pakkal. According to the doctors, TB remains an important cause of fever, especially when it occurs outside the lungs. Dr.Pakkal continues, “Only in a very advanced stage, it may come up on the blood test. But the moment you start the patient on ATT and he responds, you know you have hit the target and reached the diagnosis.”
What if the patient does not respond to ATT either? “If he does not respond to this within a week or ten days, we stop the treatment and look to the less common causes of fever, the rarer problems like Connective Tissue Disorder (CTD) and tumors. If there is still no response and the fever continues and if the patient is over 45-50 years of age, we think in terms of deep seated tumours.”, explains Dr.Pakkal.
But what about drugging the patient through the course of hitting the right diagnosis? Can this itself not lead to drug-induced fever? “Yes, this can happen sometimes,” agrees Dr.Pakkal. “We have to think on the lines of a particular problem and treat accordingly. There is a likelihood that the patient may have a side effect from the drugs given. Fever medicines can cause gastritis or there could be a lot of body pain along with fever for which we give non-steroidal anti-inflammatory medicines like brufen which can cause gastric imbalances. Also, sometimes, it does happen that the patient is subject to a slightly higher dose than required, or is under medication for a longer stretch of treatment than required. Yes, it is also possible that patients get overloaded with drugs, leading to renal shut down or liver problems. But then it’s like a double edged sword and we have to give it a try. Every patient of FUO is a challenge in itself. Alternatively, the doctor decides to stop all medication and proceeds to do further investigative procedures or not give any treatment at all till the right diagnosis is struck.”
Dr.Mousa exercises caution in treating such patient. “You cannot say from the first time examination that this is the disease the patient is suffering from, in the case of FUO. So there is no hurry to rush into treatment. A complete investigation is necessary. For instance, there may be a reduced white blood count and we may not know whether it’s on account of the disease itself or because of the antibiotics we have given! Again, some patients may, for instance, have diarrhoea as a symptom of the disease itself, or as a side effect from the drugs they’re taking. These situations compound the problem of hitting the right diagnosis. However, sometimes we are forced to give empirical treatment before pinpointing the real problem because patients ask for treatment and in the process jump from doctor to doctor without reaching any proper diagnosis. Again, we may give patients empirical treatment since there may be a high suspicion of malaria, for example.”
Can it happen that FUO goes completely undiagnosed and lead to fatalities? With the kind of diagnostic tools available today, this would be a very, very rare instance, an extreme end of the spectrum, reassure the doctors.